The principal objective of this research grant is to understand the mechanisms of change in the composition of the arterial wall with aging and atherosclerosis. We will focus on the metabolism of the protein and lipids of labeled lipoproteins, particularly low density lipoproteins. The metabolisms of lipoprotein proteins, phospholipid, and cholesterol, and their exchange with and net flow to arterial and other tissues will be investigated in squirrel monkeys and rabbits. The metabolism of lipoproteins by isolated cells and tissue homogenates will also be studied. The influence of nutritionally induced hyperlipidemia on those processes will also be investigated. Since we have shown that these monkeys also develop gallstones on many of our semipurified diets, we will investigate the relationships of diet and one drug (chenodegxycholic acid), of plasma and of arterial lipids to the incidence of gallstones and certain aspects of biliary metabolism. These factors in biliary metabolism include composition of hepatic and gallbladder bile, bile acid pool sizes and fractional turnover rates, and the effects of interruption of the enterohepatic circulation. We propose to study the morphology of these gallstones and certain intermediary forms. We are also investigating the relationship of phospholipid and cerebroside metabolism as an index of myelination in different parts of the rhesus monkey brain during development. Bibliographic references: Harvey, J.C., and Portman, O.W. Effects of glycerol on different primate erythrocytes and their phospholipid liposomes. Comp. Biochem. Physiol. 50C: 41-48, 1075; Portman, O.W., Osuga, T., and Tanaka, N. Biliary lipids and cholesterol gallstone formation. Advances in Lipid Research 13, 1975, Academic Press, New York.